Interventional Genomics
in Rare Diseases
We aspire to streamline the translation of genetic and genomic technologies and knowledge among rare diseases with unmet therapeutic needs. We apply genome engineering technology to dissect pathogenetic mechanisms and develop innovative therapeutic approaches for rare neuromuscular & neurological diseases.
Program I: Therapeutic genetics & disease modeling in
LAMA2-deficient Congenital Muscular Dystrophy (LAMA2-CMD)
LAMA2 protein stabilizes the basement membrane and maintains muscle architecture and nerve myelination. LAMA2-CMD patients have mutations in the LAMA2 gene, leading to muscle degeneration and neuropathy. We have demonstrated that postnatal upregulation of a compensatory gene Lama1, achieved using CRISPR activation, can ameliorate dystrophic phenotypes in a mouse model of LAMA2-CMD (Kemaladewi, Bassi et al, Nature, 2019).
Our goal is to further develop the CRISPR activation-based approach to upregulate disease modifier gene as a mutation-independent therapeutic strategy for LAMA2-CMD.
Examples of current projects under this program:
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Program II: Therapeutic genetics & disease modeling in
Snyder-Robinson Syndrome (SRS) and polyamine-related disorders
Polyamines are small and ubiquitous metabolites that regulate a multitude of cellular homeostasis and functions. We have previously found that altered polyamine metabolism contributes to the skeletal muscle pathophysiology in congenital muscular dystrophy (Kemaladewi et al, Human Molecular Genetics, 2018).
Furthermore, low skeletal muscle tone is one of the clinical phenotypes in Snyder-Robinson Syndrome, which is an X-linked recessive neurological disease caused by mutations in gene encoding spermine synthase, a key player in polyamine metabolism.
Our goal is to study the shared clinical manifestations due to perturbation of polyamine metabolism in relevant disease models, and subsequently use the knowledge to develop novel therapeutic interventions.
Examples of current projects under this program:
